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Review
. 1997;50 Suppl 1(Suppl 1):3-16.
doi: 10.1159/000113351.

Phenotypic specification of hindbrain rhombomeres and the origins of rhythmic circuits in vertebrates

A H Bass  1 , R Baker
Affiliations
Review

Phenotypic specification of hindbrain rhombomeres and the origins of rhythmic circuits in vertebrates

A H Bass et al. Brain Behav Evol. 1997.

Abstract

This essay considers the ontogeny and phylogeny of the cranial neural circuitry producing rhythmic behaviors in vertebrates. These behaviors are characterized by predictable temporal patterns established by a neuronal network variously referred to as either a pacemaker, neural oscillator or central pattern generator. Comparative vertebrate studies have demonstrated that the embryonic hindbrain is divided into segmented compartments called rhombomeres, each of which gives rise to a distinct complement of cranial motoneurons and, as yet, unidentified populations of interneurons. We now propose that novel rhythmic circuits were innovations associated with the adoption of cardiac and respiratory pumps during the protochordate-vertebrate transition. We further suggest that the pattern-generating circuits of more recent innovations, such as the vocal, electromotor and extraocular systems, have originated from the same Hox gene-specified compartments of the embryonic hindbrain (rhombomeres 7-8) that gave rise to rhythmically active cardiac and respiratory circuits. Lastly, we propose that the capability for pattern generation by neurons originating from rhombomeres 7 and 8 is due to their electroresponsive properties producing pacemaker oscillations, as best typified by the inferior olive which also has origins from these same hindbrain compartments and has been suggested to establish rhythmic oscillations coupled to sensorimotor function throughout the neuraxis of vertebrates.

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Figures

Fig. 1
Fig. 1
Hindbrain rhombomeres, sonic motor nuclei and conserved hindbrain segments. A–C Stage 23 quail embryo hindbrains viewed ventrally in either combined bright field/epifluorescence (A) or epifluorescence alone (B, C). A Rhombomeres 1–8 and spinal cord (sc) are indicated. DiI (orange) and DiA (yellow-green) applied, respectively, to right and left sides of dissected spinal cord segments at C2–3 levels revealed retrogradely labelled neurons with distinct medial (ipsilateral to injection) and lateral (contralateral) positions in the hindbrain. B Higher magnification view of panel A showing marked decrease in density of labelled neurons, especially contralaterally projecting ones (orange), at rhombomeres 6–7 boundary. C Following a unilateral C2–3 application of DiQ (red), the rhombomeres 6–7 border was sharply delineated, and small clusters of medial neurons were observed ipsilateral to the injection in rhombomeres 2–6 [methods after Gilland and Baker, 1993]. D General relationship between midbrain mesomere (m), hindbrain rhombomeres (r), spinal cord (sc), cranial nerve ‘motor nuclei’ and pattern of Hox gene (B1–B5) expression. E–G Following biocytin application to a single sonic motor nerve, transneuronal transport labels sonic motor (SMN) and pacemaker (PN) neurons bilaterally in a toadfish (E). Dextran-biotin labelling of a single nerve labels only the ipsilateral SMN (F) whereas biocytin labels the SMN and putative PNs bilaterally (G) in embryonic midshipman [1.2 and 1.8 cm; see Lindholm and Bass, 1993, and Marchaterre et al., 1993, for embryo staging; Bass et al., 1994, for adult phenotype and methods].
Fig. 2
Fig. 2
Rhythmically active vocal and electric communication systems of vertebrates. Representative oscillograph records of vocalizations of anuran (advertisement call of gopher frog, Rana capito aesopus), avian (song of loon) and teleost fish (advertisement call, ‘hum’, of plainfin midshipman, Porichthys notatus) species are illustrated; lower trace is on an expanded time scale. Also shown are electric organ discharges from ‘wave’ (Gymnarchus niloticus) and ‘pulse’ (Brienomyrus brachyistius) type, weakly electric teleosts. Line drawings show the position of a sound-generating larynx (anuran), syrinx (avian) and swimbladder (teleost fish), and electric organ [teleost, see text for details; modified from Bass, 1989]. Frog and avian recordings courtesy of D. Bodnar and the Cornell Laboratory of Ornithology, respectively.
Fig. 3
Fig. 3
Rhythmically-active vertebrate circuitry. A Vocal circuitry. Intracellular records from identified sonic motor and pacemaker neurons following midbrain stimulation in the plainfin midshipman, Porichthys notatus. Each trace is average of four sweeps; top is intracellular record, and bottom is intracranial record from left sonic occipital nerve. Small arrows at the beginning of the lower traces indicate midbrain stimulus onset. The nerve discharges were highly synchronous and aligned (vertical lines) to illustrate the relative timing between pacemaker and motoneuron firing. Time scale and direction of polarity for all records are indicated. Modified from Bass and Baker [1990]. B Electromotor circuitry. Intracellular recordings from electric pacemaker (top) and relay (bottom) neurons in a pulse gymnotoid, Hypopomus. Pacemaker cell (top) fires after the gradually rising membrane potential reaches a critical threshold. A relay cell (bottom) responds by firing a sudden action potential. The corresponding EOD is shown below each trace. Top and bottom records on the right show, respectively, superimposed traces of pacemaker and relay cells during a smooth rise in discharge frequency. Calibrations are indicated. Modified from Kawasaki and Heiligenberg [1989]. C Eye movement circuitry. Bottom: Velocity to position (Vel/Pos) integrator neurons of goldfish, Carassius auratus. The left histogram indicates firing rate (FR) during spontaneous eye movements correlated with horizontal, left eye position during fixation (LE). Neuron also exhibits sensitivity associated with fast phase of vestibular nystagmus (arrow). The right histogram shows FR of a purely position related neuron during sinusoidal head rotation (Ḣ) in the dark. Head velocity is inverted to facilitate comparison to eye velocity. The FR correlates with eye position but not eye velocity (LĖ) as illustrated by the 90° phase lag of Ḣ and LĖ (arrow) relative to FR. Calibrations are indicated. Modified from Pastor et al. [1994]. Top: Burst-driver neurons (BDNs) in cat (positioned rostral to eye velocity area II in goldfish, see bottom panel). Left histogram indicates FR during spontaneous saccadic eye movements correlated with horizontal eye position (HOR). The right histogram shows a burst of activity in association with fast phase of vestibular nystagmus (arrow). Calibrations are indicated. Modified from Kitama et al. [1992]. Abbreviations: SMN = Sonic motoneurons; PN = vocal pacemaker neurons; VM = ventral medullary nucleus [also see Bass et al., 1994]; EM = electromotoneurons; PN = electric pacemaker neurons; POS = eye position integrator neurons; VEL = eye velocity integrator neurons; BDN = burst driver neurons [also see Pastor et al., 1994]; IO = inferior olive. Anterior expression limits for Hox genes are also indicated B3–B5. D Inferior olive of guinea pig. Spontaneous bursts of spikes were recorded intracellularly from an inferior olive neuron and displayed at different sweep speeds. Top left: The neuron fired four action potentials, with the fifth (arrow) corresponding to a subthreshold somatic Ca2+ spike. Bottom left: A longer burst of spikes is shown at slower sweep speed. Top right: The action potentials shown in bottom left are superimposed at a faster sweep speed. The first action potential, which arises from the resting membrane potential level, had a slightly higher amplitude and a rather prolonged after-depolarization that was followed by a prolonged after-hyperpolarization (also see other traces). The other spikes in the train became progressively shorter until failure of spike generation occurred, terminating the burst. Bottom right: The same set of records as in bottom left showing a somatic Ca2+ spike arising from the after-hyperpolarization and the range of spike intervals in the train. Modified from Llinás and Yarom [1986]. Bottom panel: Proposed embryonic distribution of nuclei forming rhythmically-active circuits superimposed on schematic representations of rhombomere (rs) – spinal (sc) template (see fig. 1D).
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